2.50
HDL Handle:
http://hdl.handle.net/10033/98496
Title:
Stereoselective total synthesis of etnangien and etnangien methyl ester.
Authors:
Li, Pengfei; Li, Jun; Arikan, Fatih; Ahlbrecht, Wiebke; Dieckmann, Michael; Menche, Dirk
Abstract:
A highly stereoselective joint total synthesis of the potent polyketide macrolide antibiotics etnangien and etnangien methyl ester was accomplished by a convergent strategy and proceeds in 23 steps (longest linear sequence). Notable synthetic features include a sequence of highly stereoselective substrate-controlled aldol reactions to set the characteristic assembly of methyl- and hydroxyl-bearing stereogenic centers of the propionate portions, an efficient diastereoselective Heck macrocyclization of a deliberately conformationally biased precursor, and a late-stage introduction of the labile side chain by means of a high-yielding Stille coupling of protective-group-free precursors. Along the way, an improved, reliable protocol for a Z-selective Stork-Zhao-Wittig olefination of aldehydes was developed, and an effective protocol for a 1,3-syn reduction of sterically particularly hindered beta-hydroxy ketones was devised. Within the synthetic campaign, a more detailed understanding of the intrinsic isomerization pathways of these labile natural products was elaborated. The expedient and flexible strategy of the etnangiens should be amenable to designed analogues of these RNA-polymerase inhibitors, thus enabling further exploration of the promising biological potential of these macrolide antibiotics.
Affiliation:
Institut für Organische Chemie, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany.
Citation:
Stereoselective total synthesis of etnangien and etnangien methyl ester. 2010, 75 (8):2429-44 J. Org. Chem.
Journal:
The Journal of organic chemistry
Issue Date:
16-Apr-2010
URI:
http://hdl.handle.net/10033/98496
DOI:
10.1021/jo100201f
PubMed ID:
20334428
Type:
Article
Language:
en
ISSN:
1520-6904
Appears in Collections:
Publications from Dept. of Medicinal Chemistry (MCH)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorLi, Pengfeien
dc.contributor.authorLi, Junen
dc.contributor.authorArikan, Fatihen
dc.contributor.authorAhlbrecht, Wiebkeen
dc.contributor.authorDieckmann, Michaelen
dc.contributor.authorMenche, Dirken
dc.date.accessioned2010-05-11T13:06:53Z-
dc.date.available2010-05-11T13:06:53Z-
dc.date.issued2010-04-16-
dc.identifier.citationStereoselective total synthesis of etnangien and etnangien methyl ester. 2010, 75 (8):2429-44 J. Org. Chem.en
dc.identifier.issn1520-6904-
dc.identifier.pmid20334428-
dc.identifier.doi10.1021/jo100201f-
dc.identifier.urihttp://hdl.handle.net/10033/98496-
dc.description.abstractA highly stereoselective joint total synthesis of the potent polyketide macrolide antibiotics etnangien and etnangien methyl ester was accomplished by a convergent strategy and proceeds in 23 steps (longest linear sequence). Notable synthetic features include a sequence of highly stereoselective substrate-controlled aldol reactions to set the characteristic assembly of methyl- and hydroxyl-bearing stereogenic centers of the propionate portions, an efficient diastereoselective Heck macrocyclization of a deliberately conformationally biased precursor, and a late-stage introduction of the labile side chain by means of a high-yielding Stille coupling of protective-group-free precursors. Along the way, an improved, reliable protocol for a Z-selective Stork-Zhao-Wittig olefination of aldehydes was developed, and an effective protocol for a 1,3-syn reduction of sterically particularly hindered beta-hydroxy ketones was devised. Within the synthetic campaign, a more detailed understanding of the intrinsic isomerization pathways of these labile natural products was elaborated. The expedient and flexible strategy of the etnangiens should be amenable to designed analogues of these RNA-polymerase inhibitors, thus enabling further exploration of the promising biological potential of these macrolide antibiotics.en
dc.language.isoenen
dc.titleStereoselective total synthesis of etnangien and etnangien methyl ester.en
dc.typeArticleen
dc.contributor.departmentInstitut für Organische Chemie, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany.en
dc.identifier.journalThe Journal of organic chemistryen

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